Broad Antifungal Spectrum of the Pore-Forming Peptide C14R Against Cryptococcus and Candida Species from the WHO Fungal Priority Pathogens List

The World Health Organization (WHO) prioritized 19 fungal species based on the significant impact of these pathogens on human health, including the emergence of antifungal resistance, which highlights the necessity of finding new antifungal therapies. Among these novel therapeutic approaches, the antimicrobial pore-forming peptide C14R has shown to be promising against <i>Candida albicans</i> and <i>Candida auris</i>. In this study, the antifungal in vitro efficacy of C14R was assessed against six additional species from the WHO priority list, <i>Cryptococcus neoformans</i>, <i>Cryptococcus gattii</i>, <i>Candida glabrata</i>, <i>Candida tropicalis</i>, <i>Candida parapsilosis</i> and <i>Candida krusei</i>, as well as against <i>Candida dubliniensis.</i> This study shows that C14R has good antifungal activity against several clinical isolates of the studied species, with MIC values between 0.8476 and 10.88 µg/mL. Most notably, some of the studied isolates are resistant to commonly used antifungal drugs but are susceptible to the peptide. C14R showed, moreover, its capacity to disrupt <i>Cryptococcus</i> capsules, beyond its already proven capacity to disrupt plasma membranes, and its antifungal activity was not affected depending on the serotype or species assessed. The inclusion of basidiomycete and ascomycete yeasts allowed us to display the broad-spectrum potential of C14R, highlighting it as a promising candidate as an antifungal agent.